Multiple sclerosis (MS) affects more than 350.000 people in the US and 2.5 million worldwide. In the US prevalence estimates vary between 5 and 119 per 100.000 and healthcare costs are estimated to be more than $10 billion annually in the US alone. It is the most common neurological disease in young adults, with the risk of subsequent chronic functional impairment and disability after 10-15% of disease duration. The disease is characterized initially in 80-90% of patients by recurrent neurological events (relapses) that are attributable to multifocal lesions within the CNS. Further disease courses vary from benign to classical relapsing-remitting (RR), primary (PP) and secondary (SP) chronic progressive or rare fulminant disease course. MS is considered to be of autoimmune origin and is characterized neuropathologically by variable extents of focal inflammation, demyelination, axonal damage, gliotic scarring and atrophy, but also by remyelination and regeneration in the CNS. This has led, together with the clinical variability, to the concept of MS as a heterogenous disease with respect to four pathogenetic mechanisms of demyelination1,2. One of these pathogenetic subtypes is characterized neuropathologically by antibody-dependent immune mechanisms involved in the formation of MS lesions1,3.
During the past years, an important role of autoreactive B cells and autoantibodies has been demonstrated4. Recent studies uniformly showed clonal expansion of antibody-secreting B cells in the CNS and cerebrospinal fluid (CSF) of patients with MS5,6. Furthermore, detection of oligoclonal antibodies in CSF of patients with neurological diseases has been associated with the presence of MS. Numerous studies have reported the recognition of central nervous system (CNS) myelin autoantigens such as myelin basic protein (MBP), proteolipid lipoprotein, myelin oligodendrocyte glycoprotein, myelin associated glycoprotein by autoantibodies present in CSF and serum of MS patients, but also in patients with other-inflammatory neurological diseases (OIND) and non-inflammatory neurological diseases (NIND) as well as healthy controls7-11.
A physician may diagnose MS in some patients soon after the onset of the illness. In others, however, doctors may not be able to readily identify the cause of the symptoms, leading to years of uncertainty and multiple diagnoses. The vast majority of patients are mildly affected, but in the worst cases, MS can render a person unable to write, speak or walk. Unfortunately, no single laboratory test is yet available to prove or rule out MS. Therefore, there is a great need in the art for improved diagnostic tests for MS. The development of a panel of biomarkers, specific for different pathophysiological mechanisms, will be crucial for the further understanding of the pathogenesis of MS, as well as diagnosis, classification, disease activity, and theranostic applications.
In the present invention, we report the identification of autoantibody binding peptides/proteins which are highly specific for MS patients. The results obtained were also correlated to disease duration, disability and different clinical course of disease. The autoantibody profiles against these selected peptides can be used as a biomarker panel for the specific detection of MS.